crossing96/oncoscreening huggingface dataset:
Real-World Outcomes of Enfortumab Vedotin and Pembrolizumab in Advanced Urothelial Carcinoma: A Multicenter Retrospective Analysis.	INTRODUCTION: Enfortumab vedotin plus pembrolizumab has emerged as a new standard of care for previously untreated patients with advanced urothelial carcinoma following the EV-302 trial. However, data on its efficacy and safety in routine clinical practice remain limited. Herein, we evaluated real-world clinical outcomes for patients with advanced urothelial carcinoma receiving the combination as first-line or subsequent-line therapy. PATIENTS AND METHODS: This retrospective cohort study included adults (≥18 years) with histologically confirmed bladder or upper tract urothelial carcinoma (other histologic type variants were also included), who initiated treatment with enfortumab vedotin-pembrolizumab therapy between May 2020 and December 2024 at the Mayo Clinic. Patients initiating therapy after December 2024 or with incomplete data were excluded. Patients were stratified by line of therapy: Cohort A included patients who received enfortumab vedotin-pembrolizumab as first-line therapy, and Cohort B included patients who received it as subsequent-line therapy. The primary endpoint was to estimate median progression-free survival in cohort A and cohort B. RESULTS: A total of 183 patients with advanced urothelial carcinoma treated with the enfortumab vedotin-pembrolizumab combination were included. The median age at treatment initiation was 71.9 years (IQR, 64.7-77.4). Most patients were male (71.0%) and white (90.7%). The median progression-free survival was 12.9 months (95% CI, 9.5-NE) in Cohort A and 9.3 months (95% CI, 6.3-NE) in Cohort B. This difference was not statistically significant (HR, 1.30; 95% CI, 0.83-2.04; P = .246). Treatment-related adverse events of any grade were reported in 93.4% of patients, with 30.6% experiencing Grade ≥3 AEs. CONCLUSION: In this real-world cohort, enfortumab vedotin-pembrolizumab combination demonstrated meaningful clinical activity and manageable toxicity in both first-line and subsequent-line settings, consistent with results from the EV-302 trial.	bladder
Real-world impact of cisplatin-based neoadjuvant chemotherapy on bladder cancer survival: a 20-year study.	BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) is the standard of care for cT2-4aN0M0 bladder cancer (BCa) patients candidates for radical cystectomy (RC). This study examines changes in NAC administration over time and its impact on survival within a large, real-world multicenter cohort. METHODS: Our analysis included cT2-4aN0M0 BCa patients from 23 tertiary referral centers who underwent RC and pelvic lymph-node dissection with or without NAC administration between 2004 and 2024. The estimated annual percentage change (EAPC) was used to analyze the temporal trend of NAC administration and pathological complete response rates (pT0) over time. Subsequently, we relied on 1:1 propensity score matching (PSM) for age, sex, cT stage, Charlson Comorbidity Index (CCI), and smoking habit. Multivariable logistic regression (MLR) model addressed the association of pT0 and NAC exposure. Survival analyses consisted of Kaplan-Meier plots (KM) and multivariable Cox regression models (MCR) addressing cancer-specific mortality (CSM) and overall mortality (OM) according to NAC exposure. RESULTS: Overall, 3,138 patients were identified. Of these, 859 (27%) received NAC. NAC implementation increased substantially from 2004 to 2024 (EAPC: + 9.2%, p < 0.001), as well as pT0 rates (EAPC: + 7.6, p < 0.001). After 1:1 PSM (847 NAC + vs. 847 NAC-), MLR showed NAC as the strongest predictor of pT0 (OR: 2.89, p < 0.001). KM estimated 5-year CSM and OM rates of 22.5% versus 31.3% and 23.6 versus 34.5% in NAC + versus NAC-, respectively.At MCR, NAC exposure was associated with lower CSM (HR: 0.90, p = 0.01) and OM (HR:0.85, p = 0.001) rates relative to their unexposed counterparts. CONCLUSIONS: The current study demonstrated a significant increase in NAC administration over time, accompanied by higher rates of pT0 as well as improved survival among NAC-treated patients. The major limitation is represented by the retrospective nature of the study.	bladder
Multi-omics dissection of fatty acid metabolism heterogeneity identifies PRDX1 as a prognostic marker in bladder cancer.	BACKGROUND: Fatty-acid metabolism (FAM) is rewired in bladder cancer (BLCA), yet its impact on intratumoral diversity and patient outcome is unclear. METHODS: To characterize FAM heterogeneity, we integrated spatial and single-cell transcriptomic approaches. We employed high-dimensional weighted correlation network analysis (hdWGCNA) alongside five distinct enrichment methods (ssGSEA, AddModuleScore, AUCell, singscore, and UCell) to identify modules with elevated FAM activity. Subsequently, machine learning algorithms were applied to bulk RNA sequencing datasets to pinpoint the key gene with highest predictive value. This candidate underwent validation through functional experiments and analysis of clinical specimens. RESULTS: Malignant epithelial cells displayed the strongest FAM activity. Cross-platform scoring and co-expression analysis produced a refined high-FAM gene set. Integrating this signature with bulk datasets singled out PRDX1 as a key driver. PRDX1 was up-regulated in tumors, predicted poorer prognosis, and was enriched in malignant epithelial cells. Silencing PRDX1 curtailed BLCA cell proliferation, migration, and invasion. CONCLUSIONS: PRDX1 emerges as a FAM-linked oncogenic biomarker that fosters BLCA progression. These findings define the metabolic hierarchy of BLCA and nominate PRDX1 as a candidate target for personalized therapy.	bladder
Risk Score Model of Aging-Related Genes for Bladder Cancer and Its Application in Clinical Prognosis.	PURPOSE: Bladder cancer (BLCA) ranks as the tenth most common malignancy worldwide, with rising incidence and mortality rates. Owing to its molecular and clinical heterogeneity, BLCA is associated with high rates of recurrence and metastasis after surgery, contributing to a poor 5-year survival rate. There is a pressing need for highly sensitive and specific molecular biomarkers to enable early identification of high-risk patients, guide clinical management, and improve patient outcomes. This study aimed to develop a prognostic model on the basis of aging-related genes (ARGs) to evaluate survival outcomes and immunotherapy responsiveness in patients with BLCA, and to further explore its relevance to the tumor immune microenvironment and drug sensitivity. MATERIALS AND METHODS: Transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus were used to construct a 12-gene ARG-based prognostic signature through LASSO and Cox regression analyses. Patients were stratified into high-risk and low-risk groups according to the median risk score. Kaplan-Meier survival curves, receiver operating characteristic analyses, and nomograms were used to assess the predictive value of the model. Univariate and multivariate Cox regression analyses were conducted to determine its prognostic independence. RESULTS: Twelve ARGs were identified. Patients in the low-risk group exhibited significantly better overall survival (P < .0001). In the TCGA cohort, the model yielded AUC values ranging from 0.772 to 0.794 across 1-5 years. Cox regression confirmed the ARG score as an independent prognostic indicator. External validation using the GSE32894 data set supported its clinical reliability. The ARG signature was also associated with immune cell infiltration and predicted chemosensitivity. CONCLUSION: The ARG-based risk score independently predicts clinical prognosis in BLCA and correlates with immune microenvironment characteristics, offering potential value in guiding personalized treatment strategies.	bladder
The influence of immunocompromised status on recurrence and progression free survival among nonmuscle invasive bladder cancers (NMIBCs) undergoing transurethral resection of bladder tumor (TURBT) and adjuvant intravesical bacillus Calmette Guerin (BCG): Analysis of USA insurance claim data.	INTRODUCTION: Transurethral resection of the bladder tumor (TURBT) followed by intravesical Bacillus Calmette-Guérin (BCG) immunotherapy is a standard treatment for high-risk non muscle-invasive bladder cancer (NMIBC). However, due to potential risk of dissemination, current guidelines recommend caution when proposing BCG treatment in immunocompromised patients. Our aim was to assess the efficacy and safety of BCG treatment in immunocompromised patients. MATERIALS AND METHODS: Patients aged ≥18 with a diagnosis of bladder cancer (BC) who underwent BCG therapy in 2007-2021, were identified in the Merative(TM) Marketscan® Research Commercial and Medicare databases. Multivariable Cox proportion hazard regressions adjusted by relevant confounders were performed to investigate the influence of immunosuppression on the events associated with progression and recurrence of BC, both in the unmatched cohort and after 1:2 propensity score matching (PSM). Also, subgroup analysis on progression in patients without cancer other than BC was conducted. RESULTS: Immunocompromised and immunocompetent patients had similar rates of disseminated BCG infection after intravesical immunotherapy. However, immunocompromised patients had shorter progression-free survival and higher probability of progression (aHR: 1.23, 95% CI: 1.11-1.38), as well as shorter recurrence-free survival and a higher probability of recurrence (aHR: 1.13, 95% CI: 1.05-1.20). Similar significant associations were observed in the PSM cohort. A subgroup analysis of patients without any additional oncological diagnoses beyond BC confirmed a higher likelihood of progression in the immunocompromised group (aHR: 1.34, 95% CI: 1.15-1.56). CONCLUSIONS: BCG immunotherapy is safe in immunocompromised patients. Nevertheless, the efficacy of intravesical BCG in these patients might be suboptimal thus advocating the need for appropriate counselling and a possible lower threshold to consider radical treatment.	bladder
Nanomaterial-Enhanced Immunotherapy: Advancing T-Cell-Based Treatments for Bladder Cancer.	Bladder cancer (BC) is a prevalent urinary malignancy characterized by high recurrence rates and suboptimal long-term outcomes from traditional treatments such as surgery, chemotherapy, and radiotherapy. T-cell-based immunotherapy has emerged as a promising approach, harnessing T cells' capacity to target and destroy tumor cells, yet it faces challenges from the immunosuppressive tumor microenvironment (TME), immune evasion, and T-cell exhaustion. Nanomaterials offer innovative solutions by enabling targeted delivery of antigens, checkpoint inhibitors, and immunomodulators; remodeling the TME through metabolic interventions (eg, hypoxia alleviation and adenosine reduction); and enhancing T-cell infiltration and persistence with stimulus-responsive systems like pH-sensitive nanoparticles and biomimetic vesicles. This review systematically examines nanomaterial integration to amplify T-cell-mediated immunity in BC, covering T-cell origins, differentiation (eg, CD8+ cytotoxic and CD4+ helper subsets), roles in the TME, and exhaustion mechanisms driven by factors like PD-1 and TOX. We discuss key strategies including direct immune enhancement via immunogenic cell death induction, metabolic reprogramming to optimize T-cell function, and sustained activation for improved persistence. In conclusion, these nanomaterial-enhanced therapies address critical barriers, promoting precise and synergistic immune responses. Future prospects highlight AI-driven designs, personalized medicine, and clinical translation to tackle heterogeneity, biosafety, and resistance for durable BC remission.	bladder
NEAT1 is a therapeutic target for reversing T-cell exhaustion in bladder cancer.	BACKGROUND: T-cell exhaustion induced by the tumor microenvironment is an important factor in posing a major challenge to effective cancer immunotherapy. Immune checkpoint inhibitors aim to reverse T-cell exhaustion. However, the effectiveness of immune checkpoint inhibitors is often limited due to their off-target effects and single targets. Herein, we attempt to identify molecular targets that can regulate the expression of multiple immune checkpoints to reverse T-cell exhaustion. METHODS: NSG mice with xenotransplantation of human bladder cancer cells were used to investigate the function of nuclear paraspeckle assembly transcript 1 (NEAT1) in T-cell exhaustion. Chromatin isolation by RNA purification, chromatin immunoprecipitation, and luciferase assays was employed to investigate the molecular mechanisms by which NEAT1 regulates expression of target genes. RESULTS: NEAT1, a bladder cancer-related long non-coding RNA (lncRNA), promotes lactate production in tumor cells by binding to the lactate dehydrogenase A gene. This lactate production subsequently inhibits NEAT1 expression in CD8+T cells. Furthermore, NEAT1 in CD8+T cells plays a crucial role in modulating the immune response of CD8+T cells against tumor cells. Our findings indicate that NEAT1 regulates the expression of multiple immune checkpoint genes by directly binding to them and inhibiting transcription through the alteration of histone lactylation near transcriptional start sites, which affects RNA polymerase II recruitment. CONCLUSIONS: lncRNA NEAT1 serves as a modulator of the antitumor response of CD8+T cells in the bladder tumor microenvironment and may represent a therapeutic target for reversing T-cell exhaustion.	bladder
The incidence and risk factors of urinary tract infections in patients undergoing bladder tumor resection: a systematic review and meta-analysis.	AIM: To summarise the available evidence concerning the incidence and risk factors of UTIs in bladder cancer patients after surgery. METHODS: Systematic searches were conducted on PubMed, Embase, Web of Science, Cochrane Library, CINAHL, the China National Knowledge Base Database (CNKI), Wanfang Database, Vips Database (VIP), and the China Biomedical Database (Sinomed). These searches encompassed literature from the inception of each database up to March 2025. This study adhered rigorously to the PRISMA guidelines. The quality of the studies included in the review was assessed using the Joanna Briggs Institute (JBI) Centre for Evidence-Based Health Care in Australia and the Newcastle-Ottawa Scale. RESULTS: A total of 19 original studies were included in this analysis, encompassing 5,905 patients. The meta-analysis results indicated that the incidence of UTIs in patients with bladder tumor resection was 22.3% [95% CI (17.7, 27.3)]. The identified risk factors for UTIs in patients with bladder cancer after surgery include diabetes, age, preoperative catheter indwelling, Use of antibiotics before surgery, and Operation time≥90 min. CONCLUSIONS: UTIs are higher in patients who have undergone bladder tumor resection. Clinical staff should prioritize preoperative assessment and risk stratification for UTIs. They must adhere to established guidelines and recommendations regarding the prophylactic use of antibiotics before surgery, maintain strict control of patients' blood sugar levels, and manage catheters meticulously to minimize the risk of UTIs.	bladder
Nivolumab plus gemcitabine-cisplatin for previously untreated unresectable or metastatic urothelial carcinoma: an Asian subgroup analysis from the global phase 3 CheckMate 901 trial.	BACKGROUND: In the global phase 3 CheckMate 901 trial, nivolumab plus gemcitabine-cisplatin demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) for unresectable or metastatic urothelial carcinoma (UC). However, clinical benefit for patients from Asian countries remains unclear. Here, we analyzed outcomes in the Asian population from CheckMate 901. METHODS: Patients with unresectable or metastatic UC were randomized to receive nivolumab plus gemcitabine-cisplatin or gemcitabine-cisplatin alone. Efficacy including OS and PFS and safety were evaluated in the Asian population. RESULTS: A total of 133 patients (72 received nivolumab plus gemcitabine-cisplatin, and 61 received gemcitabine-cisplatin alone) were enrolled from China, Japan, South Korea, Taiwan, and Singapore between January 2018 and September 2022. The median follow-up was 27.2 months. OS and PFS favored nivolumab plus gemcitabine-cisplatin over gemcitabine-cisplatin alone (median OS, 24.0 vs. 18.9 months; median PFS, 9.5 vs. 7.2 months) with hazard ratios of 0.69 for OS and 0.53 for PFS. Similar trends towards favorable OS and PFS was found in subgroups with tumor PD-L1 expression ≥1%, and regardless of tumor origin (bladder cancer or upper tract UC). The incidence of grade ≥3 treatment-related adverse events was 63.9% with nivolumab plus gemcitabine-cisplatin and 61.4% with gemcitabine-cisplatin alone. CONCLUSIONS: Nivolumab plus gemcitabine-cisplatin showed a trend towards improved OS and PFS outcomes in the Asian population, suggesting that the combination therapy may serve as a new treatment option for patients from Asian countries who have unresectable or metastatic UC. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03036098.	bladder
[INNOVATIONS IN THERAPIES FOR BACILLUS CALMETTE-GUERIN (BCG) FAILURE NON-MUSCLE INVASIVE PATIENTS].	Bladder cancer is categorized into invasive cancer, which pathologically infiltrates the muscle layer of the bladder, and non-muscle invasive bladder cancer that does not penetrate this layer. Non-muscle-invasive bladder cancer is further stratified into risk groups based on the likelihood of disease recurrence and progression. High-risk non-muscle-invasive tumors typically undergo conventional treatment with intravesical Bacillus Calmette-Guerin (BCG) instillations. However, it is anticipated that thirty to fifty percent of patients will experience treatment failure, leading to disease recurrence or progression, necessitating radical cystectomy as the subsequent therapeutic step. Extensive endeavors are underway to explore novel treatment modalities aiming to reduce the necessity for bladder removal. Diverse treatments, both systemic and local, administered directly into the bladder, have been investigated in recent years to mitigate the need for cystectomy. This review article provides an overview of current approved therapeutic options such as combined intravesical chemotherapy with gemcitabine and docetaxel, systemic therapy with pembrolizumab, intravesical therapy with nadofaragene firadenovec, and innovative investigational treatments including TAR-200 drug-releasing supplement therapy and novel viral therapy, cretostimogene grenadenorepvec.	bladder
Time to metastasis as a prognostic factor in metastatic urothelial carcinoma: results from the ARON-2 study.	Metastatic urothelial carcinoma (mUC) may present with metastases at the time of initial diagnosis (synchronous) or develop them during follow-up (metachronous). The impact of the timing of metastasis on the outcome of mUC remains unclear. We aimed to evaluate overall survival (OS) stratified by time to metastasis (TTM) in patients receiving systemic therapy in different lines. Retrospective real-world data from the ARON-2 study were analyzed to compare patient outcomes according to TTM. Cohort 1 included 735 patients receiving first-line platinum-based chemotherapy, Cohort 2 included 1164 patients receiving second-line pembrolizumab, Cohort 3 included 588 patients receiving third-line enfortumab vedotin. TTM (synchronous vs. < 6 months, and ≥ 6 months) significantly influenced overall survival (OS) in Cohort 1 (19.2 vs. 22.3 vs. 27.4 months, p = 0.004) and Cohort 2 (14.6 vs. 15.4 vs. 21.2 months, p = 0.015), but not in Cohort 3. In the multivariable Cox analysis, TTM remained an independent prognostic parameter of poor OS in Cohort 1 (hazard ratio [HR]: 1.14, 95% confidence interval [CI] 1.02-1.27; p = 0.016) and Cohort 2 (HR: 1.12, 95% CI 1.02-1.22; p = 0.014). Our findings suggest that the TTM in mUC significantly influences OS in patients receiving first-line platinum-based chemotherapy and second-line pembrolizumab. The prognostic role of TTM should be considered in the future clinical trial designs.	bladder
Efficacy of sacituzumab govitecan after enfortumab vedotin in advanced urothelial carcinoma: Analysis of the UNITE study.	BACKGROUND: Sacituzumab govitecan (SG) is an antibody-drug conjugate used for advanced urothelial carcinoma (aUC) refractory to platinum-based chemotherapy and immune checkpoint inhibitors (ICI). Real-world data are needed to better define SG outcomes, particularly following treatment with enfortumab vedotin (EV). In this analysis, we aim to evaluate efficacy of SG after EV and assess putative biomarkers associated with outcomes. METHODS: In the UNITE retrospective study, we identified patients who received ≥1 SG cycle after therapy with EV. Observed response rate (ORR) was assessed in evaluable patients and correlated with baseline clinical characteristics and biomarkers. ORRs were compared using logistic regression, while progression free survival (PFS) and overall survival (OS) from SG start were estimated via Kaplan-Meier and Cox proportional hazard (PH) model. Biomarkers of response were evaluated in multivariate Cox PH models after accounting for relevant clinical variables. RESULTS: Among 107 patients treated with SG after EV, 97 (91%) had NGS data. Median age was 69 years, 73% were male, 33% had ≥4 prior lines of therapy, and 42% received G-CSF. ORR was 18% (95% CI: 10%-26%), median PFS 3.2 months, and median OS 6.0 months. In patients with disease control on EV, ORR was 22% compared to 8% in primary progressors on EV. No significant associations were found between molecular biomarkers and SG outcomes in the multivariate analysis. CONCLUSION: SG showed modest activity after EV in heavily pretreated patients with aUC. ORR with SG after EV was lower than reported in phase 2 and phase 3 clinical trials for SG in the postplatinum/ICI setting.	bladder
The miRNA-immune axis in bladder cancer: systematic evidence for a new era of immunotherapy precision.	INTRODUCTION: Bladder cancer (BC) is a complex disease with patients showing widely variable responses to treatment. While immunotherapy has recently emerged as a promising alternative to the standard platinum-based chemotherapy, especially for platinum-resistant tumors, clinicians still lack reliable biomarkers to predict which patients will truly benefit from immunotherapy. AIM: This systematic review aimed to explore whether miRNAs could help decode the immune landscape of BC and serve as predictive biomarkers for immunotherapy response. METHODS: A total of 3,272 articles were systematically screened on medical databases and narrowed down to 37 studies that examined the relationship between miRNAs, immune cell infiltration, and patient outcomes in BC. To further strengthen and validate our findings, we analyzed large-scale genomic data from The Cancer Genome Atlas (TCGA-BLCA). RESULTS: A total of 104 different miRNAs appeared to shape the BC immune microenvironment. Some studies also linked miRNA expression with clinical outcomes such as BCG therapy response and prognosis, while others dissected the molecular pathways. Further analyses established miR-155, miR-142, and miR-146b as key factors for CD4(+) memory T-cell and M1 macrophage infiltration. Notably, 49 miRNAs showed stage-specific expression differences in TCGA data, with 25 of them also significantly associated with progression-free interval or overall survival. CONCLUSION: miRNAs are emerging as powerful regulators of the immune microenvironment of BC. However, despite growing evidence, to date, no studies have directly explored miRNA profiles in driving immunotherapeutic decisions. Our findings highlight the need for prospective studies to translate these molecular insights into personalized treatment strategies.	bladder